On this page
- Why is folic acid prescribed with methotrexate?
- What happens if you don't take folic acid with methotrexate?
- How is folic acid usually scheduled with methotrexate?
- Should you take extra over-the-counter folic acid?
- Low-dose vs high-dose methotrexate: not the same rules
- Can methotrexate cause folate deficiency?
- When to contact your prescriber
- Frequently asked questions
- Sources
- Methotrexate works against folate pathways, so low-dose regimens for rheumatoid arthritis or psoriasis usually include prescribed folic acid.
- Prescribed folic acid can reduce stomach, mouth, liver-enzyme, and other side effects without meaningfully weakening standard low-dose treatment.
- A common U.K. regimen is 5 mg folic acid once a week on a different day from methotrexate, but your prescription is the one to follow.
- Do not add an over-the-counter folic acid product on top of prescribed folate without checking with your prescriber.
- High-dose methotrexate for cancer uses leucovorin rescue, and folic acid is not a substitute for it.
If you take low-dose methotrexate and skip your prescribed folic acid, you lose the protection it is there to provide: folic acid can reduce gastrointestinal, mouth, liver-enzyme, and other methotrexate side effects without meaningfully weakening standard treatment.12 Do not stop, skip, or change folic acid on your own; your prescriber sets the dose and day for your specific regimen.2 This page explains why the two are prescribed together, how schedules typically work, and why high-dose methotrexate is a completely different situation.
Why is folic acid prescribed with methotrexate?
Methotrexate antagonizes (works against) folate pathways in the body.12 That action is part of how it treats disease, but it can also cause side effects.
In low-dose therapy for inflammatory conditions such as rheumatoid arthritis or psoriasis, prescribed folic acid can reduce gastrointestinal, mouth, liver-enzyme, and other adverse effects without meaningfully compromising treatment efficacy in standard regimens.12 MedlinePlus notes that your doctor will probably tell you to take folic acid to decrease side effects.1
What happens if you don't take folic acid with methotrexate?
Folic acid is prescribed to lower the risk of methotrexate side effects, so not taking it removes that protective effect.21 The side effects folic acid is meant to reduce include:12
| Side effect area | Examples |
|---|---|
| Gastrointestinal | Digestive side effects 12 |
| Mouth | Mouth-related side effects 12 |
| Liver | Changes in liver enzymes 12 |
| Other | Other adverse effects listed by your prescriber 12 |
Methotrexate can also be associated with serious side effects, including blood disorders, which is one reason it needs monitoring.3
If you missed a dose
Do not double a dose after a missed tablet unless a clinician or the product instructions say to. Resume your normal schedule and ask a pharmacist when uncertain.4 If you miss doses often, or notice new mouth, stomach, or other symptoms, tell your prescriber.2
How is folic acid usually scheduled with methotrexate?
A commonly recommended U.K. regimen is 5 mg of folic acid once weekly on a different day from methotrexate, sometimes increased by the prescriber if side effects persist.2 Folic acid is usually avoided on the methotrexate day in inflammatory-disease protocols.5
Regimens vary by country, indication, methotrexate dose, kidney function, and specialist protocol.2 Follow the exact prescription rather than copying a schedule from the internet.2
| Question | General answer | Who has the final say |
|---|---|---|
| How much folic acid? | Commonly 5 mg once weekly in a U.K. regimen 2 | Your prescriber 2 |
| Which day? | Usually not the methotrexate day 5 | Your prescriber 2 |
| Can the dose increase? | Sometimes, if side effects persist 2 | Your prescriber 2 |
| Morning or night? | No established advantage for routine folic acid; condition-specific directions come first 26 | Your prescriber 2 |
For general timing questions outside methotrexate, see when to take folic acid.
Why 5 mg is different from everyday doses
A 5 mg weekly methotrexate-support dose is a treatment-specific instruction, not an everyday nutrition dose.2 Prevention doses, anemia treatment, folate support during low-dose methotrexate, and leucovorin rescue are separate uses and should not be blended into one generic dosage table.728
Should you take extra over-the-counter folic acid?
No, not without checking. Patients should not add an over-the-counter folic acid product on top of prescribed folate without checking with the prescriber.58 That includes multivitamins and B-complex products that contain folic acid.5
Anyone using prescription medicines should tell their clinician and pharmacist about all vitamins and supplements.9 Some medicines interact with methotrexate; for example, trimethoprim and other folate antagonists can interfere with folate metabolism, and the risk depends on dose, duration, other conditions, and other medicines.3
Low-dose vs high-dose methotrexate: not the same rules
Methotrexate used for cancer, ectopic pregnancy, or other high-dose indications has entirely different safety rules from low-dose inflammatory treatment.108
| Low-dose methotrexate | High-dose methotrexate (oncology and other high-dose uses) | |
|---|---|---|
| Typical conditions | Rheumatoid arthritis, psoriasis 21 | Cancer, ectopic pregnancy, other high-dose indications 810 |
| Folate used | Prescribed folic acid 2 | Folinic acid (leucovorin) rescue 8 |
| Schedule | Set by prescriber; often weekly, on a different day 25 | Precise schedules based on methotrexate exposure and lab monitoring 8 |
| Supplements | Do not add OTC folic acid without checking 5 | Supplements may interfere; oncology review is essential 118 |
Our page on folinic acid vs folic acid explains leucovorin in more detail.
Can methotrexate cause folate deficiency?
Methotrexate is one of the medicines that interferes with folate, and medicines that impair folate absorption or metabolism are a recognized cause of folate deficiency.6 Folate deficiency can cause megaloblastic anemia with fatigue, weakness, and shortness of breath.6 Because those symptoms overlap with many other conditions, testing should be guided by your clinician.12 See folic acid deficiency symptoms for more.
When to contact your prescriber
Severe allergic symptoms, breathing difficulty, or swelling need urgent medical evaluation.4 For general information on tolerability, see folic acid side effects.
Frequently asked questions
What happens if you forget to take folic acid with methotrexate?
Why can't I take folic acid on the same day as methotrexate?
How much folic acid should I take with methotrexate?
Your prescriber decides. A commonly recommended U.K. regimen is 5 mg once weekly on a different day from methotrexate, sometimes increased if side effects persist, but regimens vary by country, methotrexate dose, kidney function, and specialist protocol 2.
Can I take a multivitamin with folic acid while on methotrexate?
Check with your prescriber or pharmacist first. NHS advice is not to stack products containing folic acid on top of your prescribed folate without checking 5.
Does folic acid make methotrexate less effective?
Sources
- MedlinePlus, U.S. National Library of Medicine. Methotrexate: Drug Information.
- NHS Specialist Pharmacy Service. Using folic acid with methotrexate in rheumatoid arthritis.
- NHS Specialist Pharmacy Service. Managing interactions with methotrexate.
- NHS (UK National Health Service). About folic acid.
- NHS (UK National Health Service). Taking Methotrexate with Other Medicines and Herbal Supplements.
- NIH Office of Dietary Supplements. Folate - Health Professional Fact Sheet.
- NHS (UK National Health Service). Folic Acid: Medicine Information.
- MedlinePlus, U.S. National Library of Medicine. Leucovorin Injection: Drug Information.
- MedlinePlus Magazine, NIH. Did You Know? Supplements and Medications Can Interact in Unexpected Ways.
- MedlinePlus, U.S. National Library of Medicine. Leucovorin: Drug Information.
- Centers for Disease Control and Prevention (CDC). Folic Acid Safety, Interactions, and Health Outcomes.
- PubMed Central, NIH. Diagnosis and Treatment of Macrocytic Anemias in Adults (Nagao, 2017).
This article is for general education and is not medical advice. Doses and needs differ from person to person, so talk with your clinician or pharmacist about your situation. Read our editorial policy and medical disclaimer.
